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Regulation of the human mitochondrial chaperone mtHsp70 by the Hsp70 escort protein Hep
Author(s) -
Zhai Peng,
Silberg Jonathan Joff
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.672.1
Subject(s) - chaperone (clinical) , biogenesis , atpase , hsp70 , solubility , yeast , mitochondrion , biology , biochemistry , microbiology and biotechnology , chemistry , heat shock protein , enzyme , medicine , organic chemistry , pathology , gene
The Hsp70 escort protein Hep is required for the solubility of yeast mitochondrial hsp70 (mtHsp70) chaperones, which play central roles in protein translocation, Fe/S‐cluster biogenesis, and the stress response. To establish whether escort proteins play a similar role in metazoans, we examined the effect of human Hep on human mtHsp70 solubility and activity. We demonstrated that human Hep is localized to mitochondria like yeast Hep and showed that mtHsp70 exhibits limited solubility unless it is coexpressed with Hep. This low solubility appears to arise from aggregation mediated by the mtHsp70 ATPase domain, as this domain is only soluble when coexpressed with Hep. In vitro studies further indicate that Hep forms a tight complex with mtHsp70 (and its isolated ATPase domain) and stimulates chaperone ATPase activity. These findings provide evidence that metazoan escort proteins regulate both the catalytic activity and solubility of their cognate chaperones by interaction with their ATPase domain. Ongoing research is examining the effects of point mutations on the ability of Hep to bind mtHsp70, promote chaperone solubility, and stimulate chaperone ATPase activity.